Clinical Trials Register

Summary
EudraCT Number:	2020-002300-40
Sponsor's Protocol Code Number:	LARA4
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-11-06
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

Italy - Italian Medicines Agency

A.2

EudraCT number

2020-002300-40

A.3

Full title of the trial

TRATTAMENTO RADIOCHEMIOTERAPICO NEOADIUVANTE CON TECNICA A MODULAZIONE DI INTENSITA’ (VMAT/IMRT), BOOST SIMULTANEO INTEGRATO (SIB) E IMAGE GUIDED RADIOTHERAPY (IGRT) SEGUITO DA CHIRURGIA RADICALE NEL CARCINOMA DELLA CERVICE UTERINA LOCALMENTE AVANZATO: STUDIO PROSPETTICO DI FASE II (LARA 4.0)

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

LARA 4

LARA 4.0

A.4.1

Sponsor's protocol code number

LARA4

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	FONDAZIONE POLICLINICO UNIVERSITARIO AGOSTINO GEMELLI IRCCS UNIVERSITA' CATTOLICA DEL SACRO CUORE
B.1.3.4	Country	Italy
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	POLICLINICO A. GEMELLI ROMA IRCCS
B.5.2	Functional name of contact point	DIREZIONE SCIENTIFICA
B.5.3	Address:
B.5.3.1	Street Address	LARGO A. GEMELLI 8
B.5.3.2	Town/ city	ROMA
B.5.3.3	Post code	00135
B.5.3.4	Country	Italy
B.5.4	Telephone number	0630155701
B.5.5	Fax number	0630155701
B.5.6	E-mail	direzione.scientifica@policlinicogemelli.it

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	CISPLATINO
D.3.2	Product code	[CISPLATINO]
D.3.4	Pharmaceutical form
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CISPLATINO
D.3.9.1	CAS number	15663-27-1
D.3.9.2	Current sponsor code	CISPLATINO
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	40
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	Information not present in EudraCT
D.3.11.3.2	Gene therapy medical product	Information not present in EudraCT
D.3.11.3.3	Tissue Engineered Product	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

ADVANCED UTERINE CERVICAL CARCINOMA

CARCINOMA DELLA CERVICE UTERINA LOCALMENTE AVANZATO

E.1.1.1

Medical condition in easily understood language

ADVANCED UTERINE CERVICAL CARCINOMA

CARCINOMA DELLA CERVICE UTERINA LOCALMENTE AVANZATO

E.1.1.2

Therapeutic area

Diseases [C] - Female diseases of the urinary and reproductive systems and pregancy complications [C13]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	21.1
E.1.2	Level	PT
E.1.2	Classification code	10055094
E.1.2	Term	Cervix cancer metastatic
E.1.2	System Organ Class	10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Assessment of the histopathological complete response to the integrated treatment

Valutazione della risposta patologica completa al trattamento integrato

E.2.2

Secondary objectives of the trial

Assessment of clinical response to integrated treatment using MRI and PET-TAC imaging with 18FDG
Late and acute toxicity assessment
Assessment of local control, disease-free survival and overall survival
Evaluation of the quality of life

Valutazione della risposta clinica al trattamento integrato tramite imaging radiologico RMN e PET-TAC con 18FDG
Valutazione della tossicità acuta e tardiva
Valutazione del controllo locale, della sopravvivenza libera da malattia e della sopravvivenza globale
Valutazione della Qualità di vita

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

Other types of substudies
Specify title, date and version of each substudy with relative objectives: Validation of a predictive molecular signature of pathological response to neoadjuvant radiochemotherapy treatment in patients with locally advanced cervical cancer

Altre tipologie di sottostudi
specificare il titolo, la data e la versione di ogni sottostudio con i relativi obiettivi: Validazione di una firma molecolare predittiva di risposta patologica al trattamento radiochemioterapico neoadiuvante nelle pazienti con tumore della cervice localmente avanzato.

E.3

Principal inclusion criteria

Age =18, ECOG 0-2, histological diagnosis of cervical cancer, stage FIGO IB2- IVA (stage 2009) + positive pelvic and/or aortic lymph nodes, absence of oncological pretreatment, informed consent, sufficient medullary, renal and hepatic function

Età =18 anni, ECOG 0-2, diagnosi istologica di carcinoma della cervice uterina, stadio FIGO IB2– IVA (stadiazione 2009) + linfonodi positivi pelvici e/o aortici, assenza di pretrattamento oncologico, consenso informato, sufficiente funzionalità midollare, renale ed epatica

E.4

Principal exclusion criteria

Age <18, ECOG >3, contraindications to radiotherapy (genetic hyper-radiosensitivity syndromes), contraindications to pelvic radiotherapy: ulcerative rectocolitis, acute diverticulitis, severe diverticulosis, chronic pelvic phgosis, previous pelvic radiotherapy, patient enrolled in another experimental study, presence of internistic pathologies that contraindicate the neoadjuvant chemotherapy treatment, radiochemotherapy or surgery (severe liver disease, cardiopathy, kidney failure, etc.), presence of other neoplasm, any significant medical condition which in the opinion of the investigator may interfere with the optimal participation of the patient in the study, use of antibiotics for at least 4 weeks prior to sample collection,alcoholic patient, diseases that affect gastrointestinal motility such as scleroderma, insulin-dependent diabetes and /or uncontrolled diabetes (Hgb-A1c> 8%), clinically significant dehydration, clinically detectable ascites, sepsis.

Età <18 anni, ECOG >3, controindicazioni alla radioterapia (sindromi genetiche di iper-radiosensibilità), controindicazioni alla radioterapia pelvica: rettocolite ulcerosa, diverticolite in fase acuta, diverticolosi severa, flogosi pelviche croniche, precedente radioterapia pelvica, paziente arruolata in un altro studio sperimentale, presenza di patologie internistiche che controindichino il trattamento chemioterapico neoadiuvante, radiochemioterapico o la chirurgia (epatopatia grave, cardiopatia, insufficienza renale, ecc.), presenza di altra neoplasia, qualsiasi condizione medica significativa che secondo il parere dello sperimentatore può interferire con la partecipazione ottimale del paziente allo studio, uso di antibiotici per almeno 4 settimane prima della raccolta del campione, paziente alcolista, malattie che influenzano la motilità gastrointestinale come lo scleroderma, il diabete insulino-dipendente e / o il diabete non controllato (Hgb-A1c> 8%), disidratazione clinicamente significativa, ascite clinicamente rilevabile, sepsi.

E.5 End points

E.5.1

Primary end point(s)

Assessment of the histopathological complete response to the integrated treatment

Valutazione della risposta patologica completa al trattamento integrato

E.5.1.1

Timepoint(s) of evaluation of this end point

36 MONTHS

36 MESI

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

E.8.1.1

Randomised

E.8.1.2

Open

E.8.1.3

Single blind

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

Yes

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

103

F.4.2

For a multinational trial

F.4.2.1

In the EEA

103

F.4.2.2

In the whole clinical trial

103

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

Procedure di Follow Up

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-12-18

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-12-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2024-01-15

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